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Biomedical subjects

H Schraffordt Koops

Publications and source records attributed to H Schraffordt Koops.

At least 19 recordsLinked to original sources
PubMed1995

Hyperthermic isolated regional perfusion with cisplatin in the local treatment of spontaneous canine osteosarcoma: assessment of short-term effects.

To increase the effect of cisplatin on locoregional osteosarcoma, the short-term effect of hyperthermic isolated regional perfusion (HIRP) with cisplatin (30 mg/L extremity volume) was studied in 28 dogs with spontaneous osteogenic sarcoma, using clinical, radiological, and histological parameters. Thirty days postoperatively, mortality was 14.3%. Total platinum levels at the start of perfusion were 28.2 +/- 14.3 mg/L. A significant improvement (P < 0.001) in clinical score was observed in the overall group at 6 and 12 weeks after perfusion. The radiological parameter showed a stationary X-ray 2 weeks after perfusion and an improved X-ray 6 weeks after perfusion. Overall histological scores showed a moderate effect according to the Huvos classification. No additional therapeutic effect, according to the three parameters, could be demonstrated by increasing the perfusate temperature by 1 degrees C. HIRP with cisplatin is feasible in the local treatment of spontaneous osteosarcoma in dogs with acceptable locoregional toxicity. However, the histological results were modest, with none of the dogs showing a complete response 6 weeks after perfusion. Therefore, the search for the ideal perfusion agent with substantial contribution to the limb-sparing treatment in human osteosarcoma continues.

Animals↗
PubMed1995

A retrospective comparative study evaluating the results of mild hyperthermic versus controlled normothermic perfusion for recurrent melanoma of the extremities.

The aim of this study was to investigate the role of mild hyperthermia (39-40 degrees C) in isolated cytostatic perfusion for patients with recurrent melanoma of the extremities. A total of 218 patients treated with mild hyperthermic perfusion was compared to 166 patients perfused under controlled normothermic conditions (37-38 degrees C). Only patients whose lesions had been excised before or at the moment of perfusion were eligible for this study. A variety of prognostic factors was controlled for in a Cox proportional hazards analysis. The application of mild hyperthermia did not influence limb recurrence-free interval nor survival (corrected P values 0.46 and 0.18, respectively). In this retrospective comparative study, no benefit for mild hyperthermia in regional isolated perfusion could be identified.

Adolescent↗
PubMed1995

Decrease in pulmonary function during bleomycin-containing combination chemotherapy for testicular cancer: not only a bleomycin effect.

This study was performed to determine the changes in pulmonary function in patients randomised to receive treatment with four cycles of bleomycin, etoposide and cisplatin (BEP) (27 patients) or with four cycles of etoposide and cisplatin (EP) (27 patients) for disseminated non-seminomatous testicular cancer. This enabled us to establish whether effects other than those due to bleomycin determined the detrimental effects of BEP on lung function assessments. Slow inspiratory vital capacity (VC), the transfer factor of the lungs for carbon monoxide (TLCO), the diffusing capacity of the alveolo-capillary membrane (Dm), the pulmonary capillary blood volume (Vc) and the transfer factor of the lungs for carbon monoxide per unit alveolar volume (KCO) were determined before and at 3 week intervals during chemotherapy. Both groups, similar in terms of factors that may influence pulmonary function, showed during therapy a significant decrease in TLCO compared with the pretreatment value. Only at the end of the therapy was a significant difference in TLCO between both groups observed. Dm diminished also significantly in both groups during treatment, but differences between both groups were not seen. VC and Vc decreased in patients receiving BEP but remained constant during treatment with EP. It can be concluded that the Dm, KCO, and the widely used TLCO are not suitable parameters to monitor specifically pulmonary toxicity induced by bleomycin as part of a multidrug regimen. However, VC and Vc appear to be proper lung function assessments which reflect specifically alterations induced by bleomycin.

Adolescent↗
PubMed1995

Prediction of residual retroperitoneal mass histology after chemotherapy for metastatic nonseminomatous germ cell tumor: multivariate analysis of individual patient data from six study groups.

PURPOSE: To develop a statistical model that predicts the histology (necrosis, mature teratoma, or cancer) after chemotherapy for metastatic nonseminomatous germ cell tumor (NSGCT). PATIENTS AND METHODS: An international data set was collected comprising individual patient data from six study groups. Logistic regression analysis was used to estimate the probability of necrosis and the ratio of cancer and mature teratoma. RESULTS: Of 556 patients, 250 (45%) had necrosis at resection, 236 (42%) had mature teratoma, and 70 (13%) had cancer. Predictors of necrosis were the absence of teratoma elements in the primary tumor, prechemotherapy normal alfa-fetoprotein (AFP), normal human chorionic gonadotropin (HCG), and elevated lactate dehydrogenase (LDH) levels, a small prechemotherapy or postchemotherapy mass, and a large shrinkage of the mass during chemotherapy. Multivariate combination of predictors yielded reliable models (goodness-of-fit tests, P > .20), which discriminated necrosis well from other histologies (area under the receiver operating characteristic (ROC) curve, .84), but which discriminated cancer only reasonably from mature teratoma (area, .66). Internal and external validation confirmed these findings. CONCLUSION: The validated models estimate with high accuracy the histology at resection, especially necrosis, based on well-known and readily available predictors. The predicted probabilities may help to choose between immediate resection of a residual mass or follow-up, taking into account the expected benefits and risks of resection, feasibility of frequent follow-up, the financial costs, and the patient's individual preferences.

Analysis of Variance↗
PubMed1995

Detection of recurrence in patients with clinical stage I nonseminomatous testicular germ cell tumors and consequences for further follow-up: a single-center 10-year experience.

PURPOSE: A wait-and-see policy for patients with stage I nonseminomatous testicular germ cell tumors (NSTGCT) was evaluated in a prospective study. The frequency and time of recurrence, detection of recurrence, and presence of unfavorable prognostic factors were investigated. PATIENTS AND METHODS: During the period 1982 to 1992, 154 patients with stage I NSTGCT (median age, 29 years) underwent orchidectomy and were monitored at follow-up evaluation with physical examinations, alfafetoprotein (AFP) and beta-human choriogonadotropin (hCG) levels, chest x-rays (CXR), and computed tomographic (CT) scans of the abdomen and chest. Multivariate logistic regression analyses were performed to identify prognostic factors. RESULTS: During a median follow-up period of 7 years (range, 2 to 12), recurrence was found in 42 patients (27.3%). All cases of recurrence were detected within 2 years, 90% in the first year after orchidectomy. In 29 patients (69.0%), recurrence was detected in the abdominal lymph nodes. Nine patients (21.4%) had metastases in the retroperitoneum and mediastinum and/or lungs, and four patients (9.6%) had metastases only in the mediastinum or lungs. The majority of recurrences (97.6%) were detected by tumor markers and CT scans. Recurrence was related to the presence of vascular invasion, embryonal carcinoma (E), elevated preoperative hCG level, and absence of mature teratoma (M). Only vascular invasion was an independent risk factor. After polychemotherapy treatment for recurrence, the survival rate for the total group was 98.7%. CONCLUSION: The wait-and-see policy is a reliable method for follow-up monitoring of patients with stage I NSTGCT. Even in patients with unfavorable prognostic factors, it is justified to await the possible appearance of metastases. For the future, it is recommended that CXR be omitted from the schedule, and it might be feasible to discontinue follow-up evaluations after 5 years.

Adolescent↗
PubMed1995

[Efficacy of the tumor necrosis factor-alpha (rTNF-alpha) associated with interferon-gamma and chemotherapy in extracorporeal circulation in the limb in inoperable malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. A 4-year experience].

The authors review their experience of 4 years with isolated limb perfusion for the application of high dose TNF-alpha associated to IFN-gamma and melphalan for the treatment of regionally advanced tumours such as malignant melanoma, soft tissue sarcoma and epidermoid carcinoma. In malignant melanoma, the complete remission rate reaches 91%. In irresectable soft tissue sarcoma, this treatment when used as a neoadjuvant treatment saves the limb from amputation in 87.5% of the cases. Similar results are obtained for epidermoid carcinoma. With the regional application of high doses of TNF-alpha associated to chemotherapy and IFN-gamma, it has been possible to validate the concept of a strategy based on a dual targeting, that is the selective impact of the intratumoral vessels by TNF-alpha and of the tumour cells by chemotherapy. This approach appears to be the treatment of choice for locally advanced tumours of the limbs. However, as a single therapy, this procedure should be considered in melanoma as an induction therapy, and in sarcoma, as a preoperative treatment.

Antineoplastic Agents, Alkylating↗
PubMed1994

Rationale for using TNF alpha and chemotherapy in regional therapy of melanoma.

Recombinant tumor necrosis factor-alpha (rTNF alpha) has potent antitumor activity in experimental studies on human tumor xenografts. However, in humans, the administration of rTNF alpha is hampered by severe systemic side-effects. The maximum tolerated dose ranges from 350 to 500 mg/m2, which is at least 10-fold less than the efficient dose in animals. Isolation perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response, compared with 52% after ILP with melphalan alone. Release of nanograms levels of TNF alpha in the systemic circulation was evident but control of this leakage and appropriate intensive care resulted in acceptable toxicity. Angiographic, immunohistological, and immunological studies suggest that the efficacy of this protocol is due to a dual targeting: rTNF alpha activates and electively lyses the tumor endothelial cells while melphalan is mainly cytotoxic to the tumor cells. ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in man.

Animals↗
PubMed1994

Functional morbidity of hyperthermic isolated regional perfusion of the extremities.

BACKGROUND: Isolated regional perfusion (IRP) of an extremity is a major operation. The therapeutic value for stage I melanoma is still controversial and is presently being investigated in a prospective, randomized study by the European Organization for Research and Treatment of Cancer. So far there are no reliable data available concerning the morbidity of IRP. Therefore, we performed a prospective, randomized study on this topic. METHODS: In a prospective study, a group of 97 patients with a stage I melanoma localized on an arm or leg were randomized for IRP with melphalan followed by wide excision (WE) and fasciotomy or for WE only. Morbidity was evaluated on the basis of the following parameters: duration of hospitalization, postoperative pain, postoperative performance, and grade of perfusion toxicity. At 12-month follow-up, a physical diagnostic examination was performed to measure the mobility of the joints, and the circumference and volume of the treated and untreated extremities. RESULTS: All the parameters, including the physical diagnostic examination, could be evaluated in 83 of the 97 patients (8 patients died of metastatic disease and 1 patient died of another disease before they could be investigated; 2 patients were in too poor physical condition due to metastases to be examined, and 3 patients were unable to participate for nonmedical reasons). Age and sex distribution were comparable in the various patient groups. Treatment mortality was 0%. There were no complications except for urine retention (one patient) and wound dehiscence (one patient). After IRP + WE of the lower limb, the period of hospitalization was an average of 1.9 days longer (p = 0.01) than for WE on the limb only. This difference was absent for the arm. Naturally after perfusion, there was a significant difference in toxic reactions (edema and pain) between the IRP + WE patients and the WE-only patients. However, at 12-month follow-up, the difference in morbidity between IRP + WE and WE-only patients was no longer present: Morbidity of joints and circumference of the limb were the same. A number of subjective complaints were encountered fairly often after IRP + WE (e.g., pricking sensations or pain during changes in the weather), which can possibly be explained by fibrosis caused by perfusion. These complaints were not quantified further because they did not hinder the patients' functioning. CONCLUSIONS: In a long term, IRP with fasciotomy does not cause any additional morbidity. Immediately after the operation, there was more morbidity as a result of the perfusion, which caused a 2-day-longer period of hospitalization in the patients with lower-limb perfusion compared with those who underwent WE only. These findings are in contrast to those in the literature, in which 25% limitation of motion in the ankle joint after perfusion is mentioned. One explanation may be that we always performed fasciotomy after perfusion to prevent (sub)clinical compression syndrome and avoid late fibrosis.

Adult↗
PubMed1994

Cytogenetics as a tool in the histologic subclassification of chondrosarcomas.

Chondrosarcomas are a heterogeneous group of bone neoplasms of which the basic neoplastic tissue is cartilaginous. Frequently the histologic diagnosis and grading of chondrosarcomas is difficult and the histologic appearance does not always reflect the biologic behavior of these tumors. Therefore, it is important to find other parameters that can be of help in the proper diagnosing and grading of these neoplasms. To this end, we attempted to correlate the chromosomal pattern of chondrosarcomas to their histologic subtypes and grades. The cytogenetic analysis of two intermediate-grade chondrosarcomas of bone, and a review of the literature, are presented.

Bone Neoplasms↗
PubMed1994

Clinical experience with high-dose tumor necrosis factor alpha in regional therapy of advanced melanoma.

Isolated perfusion of the limbs (ILP) allows the delivery of high dose rTNF alpha in a closed system with acceptable side-effects. A protocol with a triple-drug regimen was based on the reported synergism of rTNF alpha with chemotherapy, with interferon-gamma, and with hyperthermia. In melanoma-in-transit metastases (stage IIIA or AB) we obtained a 91% complete response compared with 52% after ILP with melphalan alone. Leakage and release of nanograms levels of TNF alpha in the systemic circulation can be abrogated in most patients by low pump flow, continuous leak monitoring, extensive washout, and limb massage. In case of unavoidable leakage, appropriate intensive care results in minimal toxicity. The ILP with rTNF alpha appears to be a useful model for studying the biochemotherapy of cancer in humans.

Animals↗
PubMed1994

Isolated perfusion of the limb with high-dose tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma) and melphalan for melanoma stage III. Results of a multi-centre pilot study.

We report an update of a multi-centre pilot study previously published. Fifty-three patients (42 women, 11 men) were accrued between October 1988 and May 1992: 34 had stage IIIA, 15 had stage IIIAB, and four had stage IV melanoma. Most of them had more than five in-transit metastases; 50% had been previously treated by regional chemotherapy. Protocol included 90-min isolation perfusion at 40 degrees C with 2-4 mg rTNF-alpha, 0.2 mg rIFN-gamma and 10/13 mg/l melphalan. We prevented severe TNF systemic side effects by administration of dopamine and fluid loading. There has been no toxic death and the toxicity remained acceptable, with only one multi-organ failure (MOF) and no prolonged shock. Response rates remained very high, with 90% complete remission, 10% partial response and no failure. With a median follow-up time of 26 months, there were 12 regional recurrences, 15 distant metastases and nine local and distant recurrences. The median overall survival has been 28 months. We conclude that high-dose rTNF-alpha associated with melphalan in isolation perfusion is the therapy of choice for in-transit melanoma metastases.

Adult↗
PubMed1994

Development and test of an extendable endoprosthesis for bone reconstruction in the leg.

A malignant bone tumour may develop in the femur of a child. In the majority of cases it will be necessary to resect the bone involved, growth plate and adjacent tissues. A modular endoprosthetic system has been developed which can be extended non-invasively to bridge the defect resulting from such a resection. Elongation is achieved by using an external magnetic field. In vitro tests with a prototype showed that the lengthening element met all requirements. Six animal experiments showed that the lengthening element also functioned in vivo.

Animals↗
PubMed1994

The tumor microenvironment: possible role of integrins and the extracellular matrix in tumor biological behavior of intratubular germ cell neoplasia and testicular seminomas.

In the present study, we examined the distribution of integrin subunits and extracellular matrix proteins in normal testis, intratubular germ cell neoplasia (ITGCN), and primary and metastatic seminomas. Compared to normal testis in ITGCN, Sertoli cells showed increased expression of alpha 3, alpha 6, and beta 1 integrin subunits. Malignant intratubular germ cells stained for alpha 3, alpha 6, and beta 1 integrin subunits. Progression of ITGCN to invasive seminoma was associated with loss of alpha 3 integrin subunit expression by tumor cells. Consequent to this loss, it can be speculated that the strong expression on ITGCN may be related to the noninvasive character of the lesion as is also known from other noninvasive tumors. All tumors showed a strong expression of alpha 6 and beta 1 integrin subunits. The alpha 5 integrin subunit was weakly expressed in primary seminomas in all stages. No differences were observed in integrin expression between primary and metastatic tumors. The distribution of extracellular matrix proteins was heterogeneous and revealed clear architectural differences between seminomas that may reflect different stages of tumor stroma formation. To our knowledge, the results presented in this study provide the first information on the possible role of tumor-extracellular matrix interactions in the biological behavior of ITGCN and testicular seminomas.

Extracellular Matrix Proteins↗
PubMed1994

Positron emission tomography with fluorine-18-fluorodeoxyglucose for the evaluation of therapeutic isolated regional limb perfusion in a patient with soft-tissue sarcoma.

METHODS: The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. RESULTS: PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. CONCLUSION: FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.

Chemotherapy, Cancer, Regional Perfusion↗
PubMed1993

Cytogenetic abnormalities and clinical stage in testicular nonseminomatous germ cell tumors.

To study the impact of chromosomal abnormalities on the clinical behavior of testicular nonseminomatous germ cell tumors (TNSGCTs), we compared the chromosomal constitution of primary tumors of patients who initially presented and remained without metastases to those with metastatic disease. Furthermore, the chromosomal pattern of primary TNSGCTs was compared to ploidy and the clinicopathologic risk factors histology and small-vessel invasion. The modal chromosome number and the ploidy were in agreement. No correlation was found between the modal chromosome number and histology, presence of vascular invasion, or clinical stage. No correlation was found between structural chromosome abnormalities, like the number of copies of the i(12p) chromosome, and clinical stage. No obvious differences were found in chromosomal constitution of metastatic and non-metastatic tumors. The results of the present study suggest that in TNSGCTs differences in clinical behavior are not associated with gross chromosomal differences.

Adult↗
PubMed1993

Toxicity of hyperthermic isolated limb perfusion with cisplatin for recurrent melanoma of the lower extremity after previous perfusion treatment.

BACKGROUND: Hyperthermic isolated limb perfusion (HILP) has been shown to be effective for locoregional metastases or local recurrent disease. Locoregional recurrences after previous HILP is an unsolved problem. METHODS: HILP with cisplatin, 20-30 mg/l perfused limb volume, was performed in seven patients with recurrent melanoma (five with Stage IIIA and two with Stage IIIAB) after previous HILP with melphalan with or without dactinomycin. A cisplatin perfusion without local excision was performed in four patients; this treatment resulted in two complete responses and one partial response. In three patients, a cisplatin perfusion was performed with local excision of the in-transit metastases. RESULTS: During a median follow-up of 20 months (range, 10-25 months), in five (83%) patients the tumor recurred locally after a median period of 5 months (range, 3-11 months). No systemic toxicity was observed. Local toxicity consisted of postperfusion edema and neurotoxicity in all patients. The edema resolved within 2 weeks, which was in contrast to persistent neurotoxicity. A severe motor-sensory neuropathy was observed in three (43%) patients and mild sensory neuropathy in four (57%) patients. CONCLUSIONS: The severe neurotoxicity and the high local recurrence rate do not justify the use of HILP with cisplatin for recurrent melanoma after previous HILP with melphalan with or without dactinomycin.

Aged↗